Ketoprofen is a non-steroidal composition that has long been recognized as being useful in the treatment of pain, inflammation, and fever. More particularly, ketoprofen has been found in clinical studies to be very effective in the treatment of the signs and symptoms of rheumatoid arthritis, osteoarthritis, mild to moderate pain, fever, and primary dysmenorrhea, among other things. Ketoprofen is at least as effective as other available high potency compounds, such as indomethacin and phenylbutazone, but without their attendant side effects, such as increased toxicity. Also, ketoprofen is obtainable over the counter in certain dosages, whereas other high potency compounds are not.
There currently are no liquid or semi-solid ketoprofen products available on the market. There is, however, a great unfulfilled need for a liquid or semi-solid analgesic having fever reducing and anti-inflammatory properties which is safe, effective, and capable of being formed into a pharmaceutically elegant product. Three compositions tried in the past are aspirin, acetaminophen, and ibuprofen. Applicant has identified several disadvantages in using these compositions as compared with using ketoprofen. First, the analgesia produced by a given amount of aspirin, acetaminophen, or ibuprofen is less than that produced by the same amount of ketoprofen. Second, acetaminophen compositions lack anti-inflammatory activity. Third, aspirin compositions produce significant gastrointestinal distress in some patients. Fourth, aspirin has been reported linked to Reye's syndrome in children. Fifth, acetaminophen has been reported to cause liver failure in some patients and has been more recently questioned about its possible link to renal disorders. Sixth, although ibuprofen could be a drug of choice, ketoprofen in lower dosages has the same positive effect as ibuprofen; also, ibuprofen can involve gastrointestinal side effects, although less than those associated with aspirin.
Furthermore, it has come to the Applicant's attention that in children and infants, there is a need for a fever reducing composition with the benefit of an anti-inflammatory effect.
Although ketoprofen has significant advantages over aspirin, acetaminophen, and ibuprofen, there are notable problems in preparing satisfactory dosage forms of ketoprofen. This is because ketoprofen is insoluble in water, has very bitter taste, and is unstable in aqueous media. Applicant has essentially solved all of these problems by finding a way to dissolve ketoprofen in pharmaceutically acceptable solvents and make pharmaceutically acceptable liquid and semisolid dosage forms of ketoprofen. For example, Applicant has developed a method of preparing and using alkali metal salts of ketoprofen to create novel dosage forms of ketoprofen. These salts are easily dissolved in water, they permit preparation of pharmaceutical compositions which are virtually lacking in the unpleasant taste sensations of ketoprofen, and they are stable in aqueous media. They are more easily absorbed by the body and they involve less gastrointestinal distress than conventional anti-inflammatory compositions.
Dosages of ketoprofen have been available in the market place only in solid form such as in a tablet or a capsule form. There are significant segments of the population, however, who are unable to conveniently take medication in solid form. These include the pediatric population, the geriatric population, the infirm, and those who for whatever reason cannot or prefer not to swallow solid dosages of medication. For these people, the benefits of ketoprofen have been effectively unavailable because of the unavailability of liquid or semisolid forms of the composition. Until this time, attempts to meet the needs of these people involved use of other analgesic compositions in liquid forms such as liquid acetaminophen. The acetaminophen compositions lack anti-inflammatory activity, however. Aspirin has come into disfavor because it causes gastrointestinal discomfort in some patients and it reportedly has been linked to Reye's syndrome in children.
Efforts to create liquid formulations of 2-arylproprionic acids such as ketoprofen, allegedly through the “salification” of ketoprofen in aqueous vehicles, have been a failure. The formulations created have been so unstable that the constituents of the formulation must be kept physically separate until the time of administration to the patient or they must be kept away from light in an inert atmosphere such as nitrogen, helium, argon, or mixtures of two or more such inert gases. See U.S. Pat. No. 5,895,789.
Applicant has invented a number of beneficial ibuprofen compositions. His U.S. Pat. No. 4,859,704 refers to various liquid ibuprofen formulations and his U.S. Pat. No. 4,861,797 refers to various compositions involving the alkali metal salt of ibuprofen. These patents, however, do not show or suggest the novel ketoprofen compositions and dosage forms and the processes of making them disclosed and claimed in this application.